Understanding and Expanding Zinc Cation/Amine Frustrated Lewis Pair Catalyzed C–H Borylation

[(NacNac)Zn(DMT)][B(C6F5)4], 1, (NacNac = {(2,6-iPr2H3C6)N(CH3)C}2CH), DMT = N,N-dimethyl-4-toluidine), was synthesized via two routes starting from either (NacNac)ZnEt or (NacNac)ZnH. Complex 1 is an effective (pre)catalyst for the C–H borylation of (hetero)arenes using catecholborane (CatBH) with H2 the only byproduct. The scope included weakly activated substrates such as 2-bromothiophene and benzothiophene. Computational studies elucidated a plausible reaction mechanism that has an overall free energy span of 22.4 kcal/mol (for N-methylindole borylation), consistent with experimental observations. The calculated mechanism starting from 1 proceeds via the displacement of DMT by CatBH to form [(NacNac)Zn(CatBH)]+, D, in which CatBH binds via an oxygen to zinc which makes the boron center much more electrophilic based on the energy of the CatB-based LUMO. Combinations of D and DMT act as a frustrated Lewis pair (FLP) to effect C–H borylation in a stepwise process via an arenium cation that is deprotonated by DMT. Subsequent B–H/[H-DMT]+ dehydrocoupling and displacement from the coordination sphere of zinc of CatBAr by CatBH closes the cycle. The calculations also revealed a possible catalyst decomposition pathway involving hydride transfer from boron to zinc to form (NacNac)ZnH which reacts with CatBH to ultimately form Zn(0). In addition, the key rate-limiting transition states all involve the base, thus fine-tuning of the steric and electronic parameters of the base enabled a further minor enhancement in the C–H borylation activity of the system. Outlining the mechanism for all steps of this FLP-mediated process will facilitate the development of other main group FLP catalysts for C–H borylation and other transformations.


S2. Initial computational data at level used in previous reports
The calculation was performed using the Gaussian09 series of programs. 5 Geometry optimisations were completed with the B3PW91 6 functional. Calculations were run with a 6-311G(d,p) (for H, B, C, N, O, F) basis set and a LANL2DZ (for Zn) basis set. The optimization was full, with no restrictions. Stationary points located in the potential energy surface were characterized as minima (no imaginary frequencies) by vibrational analysis. Solvent effects of the chlorobenzene were introduced using the self-consistent field approach, by means of the integral equation formalism polarizable continuum model (IEFPCM). 7 NacNacZn-HBCat      Note multiple attempts to obtain solid material from these reactions failed, with either oils or clathrates formed. Furthermore, several attempts were made to perform mass spectrometry on this compound, but due to its sensitivity these all did not show the [M] + .     (41 mg, 0.05 mmol) and dissolved in PhCl (1 mL), causing rapid evolution of gas, before addition of 2-bromothiophene (49 µL, 0.5 mmol) and catecholborane (107 L, 1.00mmol).
Product was synthesised according to general procedure A and conversion versus an internal standard then determined (CH2Br2 35 µL, 0.5 mmol). Conversion to the boronic acid pinacol ester then was achieved by drying of the reaction mixture in vacuo before dissolving in DCM (0.5 mL) and reacting with a 1M solution of pinacol in NEt3 (0.75 mL, 0.75 mmol) for 1 hr at room temperature. The reaction mixture was then extracted using (ca. 5 mL) a 9:1 mixture of pentane:ethyl acetate and filtered through a (ca. 5 cm) silica plug, further (ca. 5 mL) pentane:ethyl acetate solution was used to ensure the product eluted through the plug. The eluent was then dried in vacuo and redissolved in CDCl3 allowing confirmation of the initial product as 2-methyl-5-(1,3,2-benzodioxaborole)-thiophene by comparison to the literature. 9    Product was synthesised according to general procedure A and conversion versus an internal standard then determined in-situ using mesitylene (70 µL, 0.5 mmol). Conversion to the boronic acid pinacol ester then was achieved by drying of the reaction mixture in vacuo before dissolving in DCM (0.5 mL) and reacting with 1M solution of pinacol in NEt3 (0.75 mL, 0.75 mmol) for 18 hrs at room temperature. The reaction mixture was then extracted using (ca. 5mL) a 9:1 mixture of pentane:ethyl acetate and filtered through a (ca. 5cm) silica plug, further (ca. 5mL) pentane:ethyl acetate solution was used to ensure the product eluted from the plug. The eluent was then dried in vacuo and redissolved in CDCl3 allowing confirmation of the initial product as mono borylated 2-isomer and diborylated 2,5-(1,3,2-    HBCat (2 eq.) PhCl, 80°C, 60hrs

S Br
Yield: 77% by integration against an internal standard.
The borylated product was synthesised according to general procedure A. Conversion was determined relative to CH2Br2 as internal standard (35 µL, 0.5 mmol). Conversion to the boronic acid pinacol ester then was achieved by drying of the reaction mixture in vacuo before dissolving in DCM (0.5 mL) and reacting with 1M solution of pinacol in NEt3 (0.75 mL, 0.75 mmol) for 18 hrs at room temperature. The reaction mixture was then extracted using (ca. 5mL) a 9:1 mixture of pentane:ethyl acetate and filtered through a (ca. 5cm) silica plug, further (ca. 5mL) pentane:ethyl acetate solution was used to ensure the product eluted from the plug. The eluent was then dried in vacuo and redissolved in CDCl3 allowing confirmation of the initial product as 2-bromo-5-(1,3,2-benzodioxaborole)-thiophene by comparison to previously reported literature. 11
Product was synthesised according to general procedure A. Yields were examined in-situ relative to an internal standard.
Two reactions were run with 10 min and 1 hour reaction time, the latter of which was converted to the boronic acid pinacol ester. Conversion to the boronic acid pinacol ester was achieved by drying of the reaction mixture in vacuo before dissolving in DCM (0.5 mL) and reacting with 1M solution of pinacol in NEt3 (0.75 mL, 0.75 mmol) for 18 hrs at room temperature. The reaction mixture was then extracted using (ca. 5 mL) a 9:1 mixture of pentane:ethyl acetate and filtered through a (ca. 5 cm) silica plug, further (ca. 5 mL) pentane:ethyl acetate solution was used to ensure the product passed through the plug. The eluent was then dried in vacuo and redissolved in CDCl3 allowing confirmation of the initial products as N-methyl-3-(1,3,2-benzodioxaborole)-indole and N-methyl-5-(1,3,2benzodioxaborole)-indoline by comparison to previously reported literature. 12,13 Product ratio after silica plug is 39:61 3-BCat-indole:5-BCat-indoline due to partial proto-deborylation (formation of N-methyl-indole observed by NMR) Figure S19: Borylation of N-methylindole in PhCl after 10 mins at 80°C with CH2Br2 internal standard as observed by 1 H NMR spectroscopy.
Product was synthesised according to general procedure A. Conversion was examined in-situ    HBCat (2 eq.) PhCl, 100°C, 36hrs S Yield: 37% by integration against an internal standard.
Product was synthesised according to general procedure A. Conversion was examined relative to CH2Br2 internal standard (35 µL, 0.5 mmol). Conversion to the boronic acid pinacol ester was achieved by drying of the reaction mixture in vacuo before dissolving in DCM (0.5 mL) and reacting with 1M solution of pinacol in NEt3 (0.75 mL, 0.75 mmol) for 18 hrs at room temperature. The reaction mixture was then extracted using (ca. 5mL) a 9:1 mixture of 31 pentane:ethyl acetate and filtered through a (ca. 5cm) silica plug, further (ca. 5mL) pentane:ethyl acetate solution was used to ensure the product eluted from the plug. The eluent was then dried in vacuo and redissolved in CDCl3 allowing confirmation of the initial product as 2-bromo-5-(1,3,2-benzodioxaborole)-thiophene by comparison to previously reported literature. 16 Figure S32: Borylation of benzothiophene in PhCl with CH2Br2 internal standard as observed by 1 H NMR spectroscopy.        A J Young's NMR tube was charged with NacNacZnEt (26 mg, 0.05 mmol) and dissolved in PhCl

S8. Thermal stability tests
NacNacZnH A J Young's NMR tube was charged with NacNacZnH (24 mg, 0.05 mmol) before dissolution in C6D6. The reaction was then heated for 18 hours at 80°C and monitored by 1 H NMR spectroscopy. Figure S44: (Red): NacNacZnH in C6D6 as observed by 1

S10. Computational details: Mechanistic Studies
All geometry optimizations were run with Gaussian16 (Revision A.03) 18 using the BP86 functional. 19,20 Zn centers were described with the Stuttgart RECPs and associated basis sets 21 and 6-31G** basis sets were used for all other atoms. 22,23 Stationary points were characterized with analytical frequency calculations. Transition states (one negative frequency) were characterized via IRC calculations and subsequent geometry optimizations to confirm the adjacent minima. Final free energies were computed using the triple-ζ basis set Def2-TZVP 24,25 and include corrections for dispersion using the D3BJ method 26 and solvation with chlorobenzene as determined by the experimental conditions. 27 Computed geometries and energies are shown below and all geometries are also supplied as a separate XYZ file.

Alternative mechanism
An alternative mechanism for the borylation of N-methylindole was considered where the latter is activated by the [ZnNacNac] + cation to then undergo metathesis with HBcat. The C-H activation step is kinetically accessible but endergonic, while the metathesis is inaccessible due to a high barrier of 26.6 kcal/mol, TS(L-M).